title: M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun.
abstract: Increasing evidence suggests tumor-associated macrophages (TAMs) are polarized M2 subtype of macrophage that exerts pro-tumor effects and promote the malignancy of some cancers, but the concrete mechanism is not well defined. Our previous research exhibited that proto-oncogene AP-1 regulated IL-6 expression in macrophages and promoted the formation of M2 macrophages. In this study, we investigate whether extra-cellular stimulus M-CSF help this process or nuclear factor NFκB has a synergistic role in the activation state of polarized M2 subtype of macrophage. RAW 264.7 macrophage and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. Being co-cultured with 4T1 or its supernatant, the expression of c-Jun, the member of AP-1 family, has a dramatically increase both on the level of gene and on the protein in RAW 264.7 macrophages, but the expression of c-Fos does not increase neither on the level of gene nor on the protein. After co-cultured with 4T1, RAW 264.7 has a higher consumption of M-CSF than RAW 264.7 macrophages alone. With the stimulation of M-CSF, the mRNA of c-Jun increased significantly, but decreased remarkably after adding the anti-M-CSF. And at the same time, p50, the member of NFκB family, has a similar tendency to c-Jun. WB results suggest that with the stimulation of M-CSF, p-Jun in nuclear increases heavily but decreases after the neutralizing antibody added. Coimmunoprecipitation and immunoblotting techniques confirmed that c-Jun and p50 NFκB coprecipitated, and c-Jun protein expression is properly enhanced with rM-CSF effect. In conclusion, M-CSF induces macrophage transformation by upregulating c-Jun with a certain synergy of NFκB. Our study may present a novel therapeutic strategy against cancer.
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Qin
authors.affiliation: Tianjin Medical University; Tianjin Cancer Hospital; Tianjin, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Lan
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Chengfang
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: He
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ni
authors.affiliation: School of Medicine; Nankai University; Tianjin, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D018920:Coculture Techniques; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D016173:Macrophage Colony-Stimulating Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: M-CSF; NFκB; c-Jun; co-culture; transformation